Over 400,000 deaths annually in the United States result from ischemic heart disease, most commonly due to atherosclerotic coronary artery disease (CAD). CAD affects approximately 16.8 million Americans with an estimated annual economic burden of over $165 billion. Stress cardiac imaging is the most common means of defining the presence and extent of CAD; as many as 7.5 million stress SPECT and 2.5 million stress echocardiography studies are performed each year in the U.S. The rate of false-positive and false-negative stress imaging using standard modalities averages 15%; this uncertainty in diagnosis increases costs by having to treat the sequelae of missed disease or having to perform additional, often invasive testing with attendant risks and cost. Stress imaging typically relies on detecting abnormalities in contractile or perfusion reserve, suggesting that we may improve the accuracy of stress cardiac imaging by (1) improving myocardial perfusion and wall motion image quality, (2) refining measurement of contractility and perfusion reserve, and (3) selecting better targets for ischemic heart disease (IHD) detection through improved understanding of the ischemic cascade. Combining exercise testing with CMR could fundamentally alter the current landscape of cardiac stress testing, since this approach affords for the first time measurement of myocardial perfusion, diastolic function, systolic function, electrocardiography, myocardial edema and exertional symptoms - the complete ischemic cascade - in one test. We expect that by improving both diagnostic accuracy and prognostic information, we may make a significant contribution toward improving outcomes in patients with IHD. The overall hypothesis that stress function, perfusion, and blood flow can be accurately evaluated by treadmill stress CMR will be validated by meeting the following aims: Specific Aim 1: To improve CMR methods for accurate, quantitative imaging immediately post-exercise by increasing temporal and spatial resolution and reducing the noise and artifact levels of real time imaging techniques. Specific Aim 2: To validate the accuracy of quantitative methods of measuring myocardial strain, tissue velocity, and mitral inflow velocity using real-time MRI post-exercise stress. Specific Aim 3: To test the accuracy of exercise stress CMR in patients with known or suspected coronary artery disease (CAD). The long-term objectives of this project are to improve the diagnosis and treatment of cardiovascular disease by showing that a powerful new combination of treadmill exercise stress plus Cardiac Magnetic Resonance Imaging (CMR) can safely, accurately, and non-invasively provide valuable clinical information not available with other existing stress imaging modalities. PUBLIC HEALTH RELEVANCE: Diagnosing heart disease often uses stress testing, but current methods may be inaccurate. By combining a specially-designed treadmill with a magnetic resonance imaging (MRI) scanner, we can make clearer pictures of the heart at rest and under stress conditions. This requires developing faster, high-resolution methods of imaging the heart with MRI and comparison to existing methods of stress testing. These efforts should lead to significant improvements in diagnosis of heart disease so that patients may benefit from appropriate treatment.